Dr. Clinton Wright is a neurologist and epidemiologist with an interest in the effects of vascular risk factors on cognition. These relationships are poorly understood because past definitions of vascular dementia evolved from those for Alzheimer disease. The term vascular cognitive impairment has evolved to cover the wide range of effects of vascular disease on cognition, from pure forms ranging from mild dysfunction to vascular dementia, and including those mixed with degenerative causes such as Alzheimer disease. The candidate plans a career devoted to clarifying the phenotype of vascular cognitive impairment and identifying potentially modifiable risk factors. He has a special interest in multi-ethnic populations. The hypothesis of this proposal is that exposure to vascular risk factors causes distinct patterns of cognitive dysfunction depending on the type of brain injury. Clarification of the subtypes of vascular cognitive impairment as well as the identification of imaging and biological markers and potentially modifiable risk factors has been identified as a priority area by the NINDS Stroke Progress Review Group. The specific aims of the proposed research are: 1) To determine if exposure to particular vascular risk factors and inflammatory markers is related to specific cognitive domains using a sensitive battery of neuropsychological tests. Conventional and novel risk factors will include cardiac diseases, hypertension and blood pressure, diabetes, insulin resistance and the metabolic syndrome, reported alcohol consumption, total homocysteine and inflammatory markers; and 2) To determine if cerebrovascular brain damage as measured by quantitative MRI, including white matter hyperintensity volume, subclinical infarcts, subclinical microbleeds and brain atrophy are related to specific cognitive domains, adjusting for conventional and novel vascular risk factors. Linear regression using generalized estimating equations will be carried out to examine the effect of vascular risk factors and subclinical brain disease on multiple cognitive domains simultaneously to adjust for correlation among the neuropsychological tests. The detection of vascular cognitive impairment has public health implications as the number of people with early forms before frank dementia is estimated at three million in the U.S., a number equaling the prevalence of forms with dementia.